I am a Chairperson of the Review Committee for the BLA from Ethicon for a combination fibrin sealant product with the proprietary name EVARREST.

EVARREST is a ready-to-use surgical patch composed of a flexible composite matrix (device

component) coated with human plasma-derived fibrinogen and thrombin (biological drug substances). The matrix is made of two absorbable polymers: oxidized regenerated cellulose (ORC) and polyglactin

910 (PG910). EVARREST is intended for use as an adjunct to hemostasis for soft tissue bleeding during retroperitoneal, intra-abdominal, pelvic, and (non-cardiac) thoracic surgery when standard surgical

techniques are ineffective or impractical. The review of the BLA was assigned to CBER based on the primary mode of action.

The applicant (Ethicon) requests a teleconference to discuss the proper name of their product as FDA

and Ethicon have different opinion, and requests your participation (please read the message from Jessica Chung). As an introduction to discussion, below is a summary of our position, and justification from Ethicon for an alternative term. Please let us know whether you are willing and available to participate in the teleconference (scheduled for August 23, Thursday) and to contribute to the discussion.

We had extensive internal discussions at CBER, and the Review Committee (including clinical, APLB, and Product reviewers and respective Branch Chiefs) recommends the proper name for this product to be Fibrin Sealant Patch. We have earlier established a proper name classification for combination products intended for use as adjuncts to hemostasis that consist of fibrin sealant (i.e., fibrinogen and

thrombin biological substances) and medical device (i.e., collagen in case of TachoSil, composite matrix such as PG910/ORC-based in case of EVARREST, or other supportive layers in future products).

TachoSil was the first product in this class approved in April 2010. It is our current position that the

In our opinion, the term proposed by Ethicon –b(4)----------------- implies that EVARREST has activity or interactions with the treatment site that go beyond hemostasis (which is the proposed indication for this product). Ethicon's justification (the file attached) states that the –b(4)----------- “can facilitate cellular ingrowth and regeneration of new blood vessels” and act “as an effective matrix/scaffold for tissue repair and regeneration” as demonstrated in athymic rats. While we understand the applicant's intent to highlight the role of the matrix, such “wound-healing” activity has not been demonstrated in adequate and well-controlled clinical studies. Therefore, the evidentiary standards for this claim have not been met, and we view the term –b(4)--------------- as misleading and promotional [21 CFR 202.1(e)(6) and 21 CFR 312.7]. Our analysis of proper names of FDA-approved products

shows that the use of the term "matrix" is consistently associated with "tissue or organ repair and regeneration"; "natural healing", "revascularization"; "scaffold", "cell [fibroblast] infiltration". Besides, in our opinion, the FDA-proposed term ("patch") does not exclude the contribution of the ORC/PG910 layer to the mechanism of action of EVARREST.

At the telecon, Ethicon may propose other options for FDA consideration (such as Fibrin Pad). Although the terms "pad" and "patch" are close, according to various medical dictionaries the term "patch" appears to better apply to EVARREST.

Ethicon also inquires if the proper name can be modified in the future if the "wound-healing" activity

will be demonstrated in clinical studies, and what the process would be.

We would very much appreciate your additional comments or recommendations. The dial-in information for the telecon will be sent after we receive your response.

In addition, would you be able to let me know which committee is responsible for new proper names? We would like to request the attendance of the relevant attendee(s) from that committee as we would like to understand the process for submission & review of new proposed proper names? Also, we would like to request

the attendance of David Krause from CDRH who may be able to speak to this topic?

I will be in touch with the requested information by eâ€�mail at least 48 hours before the teleconference. Thank you.

Kind Regards,

Jessica

Jessica Chung

Regulatory Affairs

Ethicon Inc., a Johnson & Johnson Company

P.O. Box 151, Route 22 West

Somerville, NJ 08876-0151

Work: 1 908 541 3828

Cell:---b(6)---------------------

Email: --b(6)---------------------------

From: Tilghman, Tracy [mailto:Tracy.Tilghman@fda.hhs.gov]

Sent: Thursday, August 16, 2012 11:45 AM

To: Chung, Jessica [ETHUS]

Cc: Shields, Mark

Subject: Teleconference to discuss the Proper name for BL#125392/0

Importance: High

Hello Jessica,

We would like to schedule a follow-up teleconference to discuss the Proper name for BL#125392/0. We would like to schedule it for Thursday, August 23rd at 9:00am EST. Please confirm this date and time

and provide conference call-in information. I have included a list of tentative attendees below.

Basil Golding

Nisha Jain Kimberly Lindsey Loan Nguyen Timothy Lee

Nancy Kirschbaum Tracy Tilghman Natalya Ananyeva

This teleconference will be a follow-up discussion of the proper name for your product (Fibrin Sealant

Patch) as you requested.

To facilitate the discussion during the teleconference, please send a list of specific questions that you plan to bring to the Agency's attention.

If you have alternative options (other than –b(4)------------------ please provide a brief justification (e.g., justify your preference for the term "pad" versus "patch").

If you seek FDA's advice regarding the future status of the proper name (i.e., after the regulatory action is made for the pending BLA), please specify your questions.

Please provide this information by e-mail at least 48 hours before the teleconference.

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